1. Field of Invention
This invention relates to delivery of biomaterial to a cell or a tissue, and more particularly it relates to delivery of biomaterial associated with particles.
2. Description of Related Art
In general, nanoparticles have been very ineffective vehicles for gene delivery, with expression levels below those seen with naked DNA. Thus, there has been relatively little progress with DNA incorporation into biodegradable sustained release particles. Also, problems encountered in gene therapy include slow accumulation and low concentration of gene vector in target tissues.
Nanoparticles formed from biodegradable polymers have been used to carry active molecules to sites in the body where the therapeutic effect is required (see Quintanar-Guerrero et al., Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. Drug Dev Ind Pharm 1998; 24:1113-28; and Kumar MNR. Nano and microparticles as controlled drug delivery devices. J Pharm Pharmaceut Sci 2000; 3:234-58). Quintanar-Guerrero et al. describe various techniques available to prepare biodegradable nanoparticles from polymers such as for example, emulsification-solvent evaporation, solvent displacement, salting-out, and emulsification diffusion. In general, such nanoparticles have limited loading capacity for most hydrophilic drugs and also are not efficient in cases where rapid accumulation of active molecules is required at their target sites.
Various studies were conducted to improve delivery of a biomaterial such as viruses (e.g., adenovirus) and plasmid DNA by physical means such as an application of a magnetic field to a vector including magnetically responsive solid phases, which are micro-to nanometer sized particles or aggregates thereof (see Plank et al., Enhancing and targeting nucleic acid delivery by magnetic force. Expert Opin Biol Ther. 2003; 3:745-58 (Plank I thereafter); Plank et al., The magnetofection method: using magnetic force to enhance gene delivery. Biol. Chem. 2003; 384:737-47 (Plank II thereafter); Scherer et al. Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther. 2002; 9:102-9).
Ito et al. describe application of magnetic granules (0.1-0.5 microns) as carriers for anti-cancer drugs administered orally in local targeting chemotherapy of esophageal cancer (see Magnetic Granules: A Novel System for Specific Drug Delivery to Esophageal Mucosa in Oral Administration. Int'l. J. of Pharmaceutics, 61 (1990), pp. 109-117). Compositions described by Ito et al. were not made as colloidal particles, and magnetic granules used therein were not stabilized.
U.S. Pat. No. 5,916,539 to Pilgrimm describes superparamagnetic particles useful in medicine for destroying tumors, increasing immunity and diagnosing conditions. The patent describes aggregates of superparamagnetic single-domain particles bearing on its surface chemically bound organic substances for further binding of active substances such as antigens, antibodies, haptens, protein A, protein G, endotoxin-binding proteis, lectins, and selectins.
Arias et al. describes an anionic polymerization procedure for preparing colloidal nanoparticles consisting of a magnetic core and a biodegradable polymeric shell wherein the polymerization medium was magnetite suspension in HCl solution (see Synthesis and Characterization of Poly(ethyl-2-cyanoacrylate) Nanoparticles with a Magnetic Core. J of Controlled Release 77 (2001), pp. 309-321).
Gómez-Lopera et al. describe preparation of colloidal particles formed by a magnetite nucleus and a biodegradable poly(DL-lactide) polymer coating by a double emulsion method, wherein aqueous suspension of magnetite particles was used to prepare an emulsion with the polymer (see Synthesis and Characterization of Spherical Magnetite/Biodegradable Polymer Composite Particles. J. of Colloid and Interface Science 240, 40-47 (2001)). It is significant that the magnetite in the cited studies was not incorporated as an organic suspension, resulting in its poor incorporation in the particle.
Plank et al. describe superparamagnetic iron oxide nanoparticles manufactured with polyelectrolyte surface coatings such as poly(ehylenimine) (PEI) and polylysine further associated with gene vectors by salt induced colloid aggregation (Magnetofection: enhancing and targeting gene delivery with superparamagnetic nanoparticles and magnetic fields. J Liposome Res. 2003; 13:29-32 (Plank III thereafter)). (See also Plank II, Scherer et al., Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo. Gene Ther. 2002; 9:102-9).
The same research group further used magnetic beads in combination with PEI and pDNA as a model of a non-viral vector mediated gene expression system for transfection of cells (see Krotz et al., Magnetofection potentiates gene delivery to cultured endothelial cells. J Vasc Res. 2003; 40(5):425-434) and delivery of antisense oligonucleotides in a catheter-based coronary angioplastic therapy for occlusive cardiovascular disease (see Krotz et al., Magnetofection-A highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo. Mol Ther. 2003; 7:700-10). The magnetic beads used by this research group lack the concept of sustained release and increased colloidal stability achievable with biodegradable polymer-based particles. Moreover, the reported results show a considerable extent of cell toxicity caused by nanoparticulate formulations (see Plank II, supra). The PEI coating stability and a possible aggregation in biological fluids have not been examined, but might potentially be a concern in these formulations.
Müller et al. studied cytotoxicity of poly(lactide), poly(lactide-co-glucolide), poly(styrene) and solid lipid particles loaded with magnetite. No attempts to incorporate magnetite as a stable organic dispersion were described (see Cytotoxicity of Magnetite-Loaded Polylactide, Polylactide/Glycolide Particles and Solid Lipid Nanoparticles. Int'l. J. of Pharmaceutics 138 (1996) 85-94). Further, the possibility of loading the particles with a drug has not been examined.
Igartua et al. describe encapsulation of magnetite particles stabilized by oleic acid in solid lipid nanoparticles (see Development and Characterization of Solid Lipid Nanoparticles Loaded with Magnetite. Int'l. J. of Pharmaceutics 233 (2002) 149-157). The authors did not address using polymer as a matrix and presented no results on drug loading in such particles.
De Cuyper et al. describe magnetoliposomes which are phospholipid bilayer coated magnetite particles prepared by adsorption of sonicated phospholipids onto magnetite stabilized by lauric acid in an aqueous solution (see Magnetoliposomes. Formation and structural characterization. Eur Biophys J 1988; 15:311-319). Such liposomes are too small to be effectively manipulated by magnetic field. Although, ability to bind drug have not been studied, the liposomes prepared by this method have limited capacity for drug substances since they can be loaded only by surface adsorption.
Messai et al. describe poly (lactic acid)-based particles ((PLA nanoparticles) surface modified by electrostatic adsorption of PEI, wherein PEI is associated with DNA (see Elaboration of Poly(ethyleneimine) Coated Poly(D, L-lactic acid) Particles. Effect of Ionic Strength on the Surface Properties and DNA Binding Capabilities. Colloids and Surfaces B: Bioninterfaces 32 (2003), pp. 293-305). PEI adsorbed onto PLA nanoparticles does not provide a stable coating and readily dissociates into the external medium upon dilution.
Sullivan et al. describe gene delivery scaffolds based on DNA plasmid condensation with colloidal gold/PEI conjugates (see Development of a Novel Gene Delivery Scaffold Utilizing Colloidal Gold-Polyethylenimine Conjugates for DNA Condensation. Gene Therapy (2003) 10, 1882-1890). Although, such conjugates when used as a vehicle for gene delivery exhibit improved size stability when compared to PEI alone, they cannot be targeted by magnetic field and lack sustained release properties.
Despite the foregoing developments, there is a need in the art for alternative means of delivery of biomaterial.
All references cited herein are incorporated herein by reference in their entireties.